The long-term objective of this study is to understand the molecular mechanism of prostate formation and maintenance. The prostate has been the subject of intense biomedical research not only because of its key role in sexual function, but more because of the high incidence of human prostate diseases. Despite the effort, one aspect that has remained poorly understood is the molecular mechanism of prostate initiation, and this is the focus of the proposed study. To date, in addition to the androgen pathway, only one signaling pathway, the Fibroblast Growth Factor (FGF) pathway has been genetically demonstrated to be essential for the initiation of all prostate buds. In this proposal, we present preliminary data suggesting that WNT signaling is essential for prostate initiation. Drawing from our recent findings in the lung, a similar branching organ as the prostate, we hypothesize that WNT function in prostate initiation is mediated through its regulation of FGF signaling. We will use advanced genetic approaches to address the relationship between these two signaling pathways in this essential first step of prostate development. This proposal defines the beginning of a long-term strategy to dissect the signaling network essential for the development and homeostasis of the prostate. PUBLIC HEALTH RELEVANCE: This proposal aims to define how WNT and FGF signaling function together to control prostate formation. As both pathways are central to stem cell maintenance and prostate tumorigenesis, our finding will provide the basis for future investigation of their interaction in prostate pathogenesis.